- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Bolut, C., Pacary, A., Pieruccioni, L., Ousset, M., Paupert, J., Casteilla, L., Simoncini, D.Machine learning (ML) models are effective at classifying images across various fields, including biology. However, their performance on biomedical images is often limited by the small size of available datasets that are constrained by the time-consuming and costly nature of experimental data collection. A review of the literature shows that many studies using biomedical images fail to follow ML best practices. This study focuses on regenerative medicine, which aims to promote tissue regeneration rather than scarring. To explore this process, […]
- by Quibod, I. L., Sciallano, C., Auguy, F., Brottier, L., Dereeper, A., Diagne, D., Diallo, A., Doucoure, H., Mayaki, S. I., Keita, I., Konate, L., Tall, H., Tekete, C., Zougrana, S., Hutin, M., Koita, O., Kone, D., Sarra, S., Verdier, V., Wonni, I., Szurek, B., Cunnac, S., Perez-Quintero, A. L.African rice (Oryza glaberrima) was independently domesticated in West Africa around 3000 years ago, and has long been intertwined in the history of the region. The gradual replacement of African rice by Asian rice (Oryza sativa), which was introduced when European settlers arrived, has since dominated rice cultivation in Africa. Domesticated rice species are affected by bacterial leaf blight (BLB), which is caused by the pathogen Xanthomonas oryzae pv. oryzae (Xoo). Here we provide evidence that the bacterial leaf blight […]
- by Koehl, A., Prillo, S., Liu, M., Xiong, J., Weng, L., Savage, D. F., Song, Y. S.Models of protein evolution are foundational to biology, underpinning essential techniques such as phylogenetic tree inference, ancestral sequence reconstruction, multiple sequence alignment, variant effect prediction, and protein design. Historically, for computational tractability, these models have relied on the simplifying — but biologically unrealistic — assumption that sites in a given protein evolve independently of each other. A crucial test of any evolutionary model is its ability to simulate realistic evolutionary trajectories, but the independent-sites assumption leads to simulations that poorly […]
- by Lee, S., Fu, Z., Choi, S.Traditional open-field assays quantify rodent behavior using low-dimensional scalar metrics that often overlook dynamical and temporally dependent aspects of spontaneous behavior. Here, we establish a high-throughput framework that integrates multi-camera 3D pose estimation from AVATAR-3D (1) with unsupervised autoregressive hidden Markov modeling using Keypoint-MoSeq (2-4) to transform recordings into time sequences of discrete, recurring behavioral units termed syllables. Drawing inspiration from information theory (5) and spectral analysis of Markov systems (6,7), we compute Shannon entropy and the second-largest eigenvalue (Eigen2) […]
- by Leonard, A. S., Pausch, H.Background: Recombination of parental haplotypes is a fundamental biological process that ensures proper segregation of homologous chromosomes and creates new combinations of alleles during meiosis. Crossover events are typically detected from large-scale pedigree-based genetic studies or linkage disequilibrium-based recombination maps, although these are generally limited to SNPs. Increasing amounts of long read sequencing and haplotype-resolved assemblies offer an alternative approach to examining recombination events at basepair resolution, albeit with much smaller sample sizes. Results: Here, we analyse five high-quality genome […]
- by Sapoval, N., Nakhleh, L.Gene tree parsimony (GTP) is a common approach for efficient reconciliation of multiple discordant gene tree phylogenies for the inference of a single species tree. However, despite the popularity of GTP methods due to their low computational costs, prior work has shown that some commonly employed parsimony costs are statistically inconsistent under the multispecies coalescent process. Furthermore, a fine-grained analysis of the inconsistency has indicated potentially complimentary behavior of duplication and deep coalescence costs for symmetric and asymmetric species trees. […]
- by Tsumagari, K., Ishihama, Y., Imami, K.Phosphoproteomics by liquid chromatography/tandem mass spectrometry requires efficient phosphopeptide enrichment, but conventional workflows are often time-consuming and prone to sample loss, particularly at low input. Here, we present Rapid Hydroxy Acid-Modified Metal Oxide Chromatography (Rapid HAMMOC), a streamlined, TiO2-based enrichment workflow that features three key improvements. First, we optimized the TiO2 column loading conditions and found that alternative pH-buffering agents and organic solvents, such as sodium bicarbonate combined with ethyl acetate, outperformed the commonly used Tris-based buffer with isopropanol. Second, […]
- by Chapman, G. B., Abutarboush, R., Connaughton, V. P.Light and transmission electron microscopy were used to identify changes in ultrastructure of the olfactory pit of larval zebrafish (Danio rerio) that occur as a result of age and altered environmental light levels. Larvae were reared under control/cyclic light or constant light condition until 4, 8, and 15 days postfertilization (dpf). The larval olfactory pit consisted of an epithelium that varies from simple to pseudostratified to stratified and contained three types of receptor cells: ciliated, microvillar and ciliated crypt. A […]
- by Heidecker, M., Mammi, P., Bergelt, T., Christ, A., Lewinski, M., Koester, T., Charon, C., Jin, Y., Marquardt, S., Blein, T., Bazin, J., Staiger, D., Crespi, M.Alternative splicing (AS) enables eukaryotes to dynamically adjust RNA and protein isoforms encoded in one gene. Long non-coding RNAs (lncRNA) have emerged as novel regulators of AS through multiple modes of action, including interactions with splicing factor (SF) proteins. Here, we used Arabidopsis thaliana lateral root development to dissect the specificity of lncRNAs in AS regulation. Data mining and a transient expression screen allowed us to identify novel lncRNAs interacting in vivo with the well-characterized SFs Nuclear speckle RNA binding […]
- by Souchay, G., Caizergues, A., Bacon, L., Champagnon, J., Devineau, O., Gelin, M., Grzegorczyk, E., Lebreton, J.-D., Plaquin, B., Pradel, R., Guillemain, M.Ringing-recoveries are an overarching element of population dynamic studies that allow estimating mortality causes and hence improve wildlife management. However, possible drawbacks of recovered rings reside in the fact that reporting probability is rarely known, but consistently lower than 100%. Thus, estimating harvest probabilities (mortality probability due to harvesting) of exploited species without knowledge of ring reporting probability by people exploiting these animals is not straightforward. We here provide the first ever reward-ring study carried out to evaluate European reporting […]
- by Hoshino, M., Nehlsen, M., Adriano Batista, R., Raphalen, M., Wakimoto, T., Uwai, S., Kogame, K., Alva, V., Coelho, S. M.Fertilization, the union of male and female gametes, is central to sexual reproduction, yet the molecular mechanisms that ensure partner recognition and enforce species specificity remain elusive. Here we identify PKN, a previously uncharacterized transmembrane protein expressed exclusively in female gametes of brown algae, as an essential determinant of fertilization. Loss of PKN abolishes fertilization without affecting earlier mating steps, including gamete attraction, placing its function as a key mediator of male-female recognition. PKN contains extracellular {beta}-propeller and mucin-like domains […]
- by Cai, H.The alignment between mutational variance, standing genetic variance, and macroevolutionary divergence in Drosophila wing shape presents a rate paradox: evolution follows mutational lines of least resistance, yet proceeds orders of magnitude slower than quantitative genetic theory predicts. Two explanations have been proposed: "deleterious pleiotropy," where stabilizing selection on unmeasured traits outside the wing morphology complex constrains evolution, and "correlational selection," where selection acts directly on trait covariances. However, recent empirical work has found little evidence of fitness costs associated with […]
- by Gomez-Munoz, C., Vittorelli, N., Gaudin, M., Agier, N., Delmas, S., Corbeau, Y., Cosentino Lagomarsino, M., Liti, G., Llorente, B., Fischer, G.Polyploidy is a ubiquitous biological phenomenon that promotes genetic innovation and adaptation1. In the budding yeast Saccharomyces cerevisiae, polyploid strains are widespread in natural, industrial, and clinical niches, yet their origin is unclear2-4. Here, we identify a novel mechanism of stepwise polyploidization that involves a Sporulate-Endoreplicate-Mate (SEM) sequence. We show that spore endoreplication during germination doubles the genome while preserving mating competence, enabling incremental increases in ploidy through mating with a non-endoreplicated spore from the same ascus. We experimentally demonstrate […]
- by Henault, M., Wood, L. M., Heasley, L. R.Aneuploidies–whole-chromosome copy number imbalances arising from nondisjunction–underlie numerous congenital and somatic disorders, but unlike many other disease-causing variants, they can readily revert back to euploidy through subsequent errors of the same type. The extent to which this inherent plasticity impacts the stability and persistence of aneuploid karyotypes in populations remains poorly understood, a gap in knowledge that continues to limit our understanding of aneuploidy-driven disease incidence, penetrance, and progression. To assess how reversion shapes aneuploid population dynamics, we developed a […]
- by Zhou, Y., Wei, C., Sun, M., Wang, L., Song, J., Xu, F., Li, Y., Zheng, W., Zhang, Y.Modeling protein conformational landscapes is essential for understanding dynamics, allostery, and drug discovery, yet existing resources lack diverse conformational coverage, energetic annotations, or benchmarking standards. ProteinConformers (https://zhanggroup.org /ProteinConformers) provides 2.7 million geometry-optimized conformations generated with a multi-seed molecular dynamics strategy, paired with 13.7 million energy evaluations and 5.5 million similarity annotations. It delivers continuous landscapes from non-native to near-native states, benchmarking framework for multi-conformation generators, and an interactive analysis platform.
- by Mulkern, A. J., Bassler, S. O., Matlock, W., Typas, A., MacLean, C.Bacterial hypermutator strains drive rapid evolution of antibiotic resistance in chronic infections. Inspired by cancer therapy approaches that exploit synthetic lethality by targeting DNA repair deficiencies in hypermutator tumours, we tested whether pairing a conventional antibiotic with a secondary DNA-damaging agent could constrain hypermutator evolution in bacteria. Using high-throughput experimental evolution of Escherichia coli repair-deficient strains, we evolved populations under carbapenem selection in combination with ciprofloxacin or mitomycin C. Strains lacking oxidative damage repair, double-strand break repair, or transcription-coupled repair […]
- by Xia, F., Baudis, M., Anisimova, M.Short tandem repeats (STRs) are a major source of genetic variation, yet their potential for genome-wide population structure inference remains underexplored. Here we present a multi-modal framework for STR-based population inference, integrating unsupervised clustering, supervised population assignment, and a novel admixture inference model, Directional Non-negative Matrix Factorization (dNMF). Applying this framework to thousands of genomes from multiple global cohorts, we first demonstrate that genome-wide STR variations provide substantially finer resolution of human population structure than single-nucleotide polymorphisms (SNPs), particularly at […]
- by Berends, E., Guimbal, S., Zhang, X., Frijns, I., van de Waarenburg, M. P. H., Scheijen, J. L. J. M., Wouters, K., van Oostenbrugge, R. J., Engelhardt, B., Foulquier, S., Schalkwijk, C. G.Background: Methylglyoxal (MGO), a highly reactive by-product of glycolysis, has been associated with cognitive decline and Alzheimer's disease, though the mechanistic role of MGO remains unclear. Moreover, conflicting findings exist regarding MGO's toxicity on the blood-brain barrier (BBB). This study investigated whether MGO can cross the BBB under physiologically relevant conditions and whether MGO affects BBB permeability. Methods: Mice were intravenously injected with highly purified home-made MGO or PBS, and MGO concentration was measured at five timepoints in the cerebral […]
- by Shahid, A., Ulrich, J.-U., Kuehnert, D.High genomic variability among viral species makes sequence classification highly dependent on multiple sequence alignment (MSA) methods, which are both computationally intensive and sensitive to data quality issues. To provide a more efficient and robust alternative, we developed DiCNN-UniK, a Dual-Input Convolutional Neural Network (DiCNN) utilizing unique k-mer signatures and universal k-mer libraries to generate novel and direct embeddings. Instead of relying on k-mer frequency patterns, DiCNN-UniK directly leverages k-mer embedding information, which provides a clear picture of local genomic […]
- by Giray, I., Ciftci, I., Farooqui, A. A.Our goals are achieved through extended task episodes. While it is well recognized that such episodes are controlled and executed as a single unit, how this is achieved remains unclear. Key observations during the execution of extended episodes (i.e., increased reaction time at episode beginnings and widespread neural activation at episode completions) have suggested that some additional, episode-related goings-on may occur at the beginning and the end. We found that when participants executed episodes of different durations, but involving trials […]